The present invention relates to dynamic charge state anionic polymers that are useful for release of cationic molecules, polyelectrolyte multilayers fabricated from them and methods of using the polymers.
Methods for the layer-by-layer assembly of multilayered polyelectrolyte films (or ‘polyelectrolyte multilayers’) provide nanometer-scale control over the structures and compositions of thin films fabricated from a broad range of cationic and anionic polymers.1-4 An evolving understanding of the structures and properties of these multilayered materials—and the ways that they can be manipulated at various length scales—has contributed to the design of functional thin films of interest in a growing number of fundamental and applied contexts.3-10 
Owing to the polyvalent nature of the electrostatic interactions in polyelectrolyte multilayers, these assemblies are frequently regarded to be ‘stable’ in physiologically relevant environments, i.e., the assemblies often do not dissolve readily or undergo large changes in macroscopic film properties when incubated in physiological media.3,5,7 9 This general stability confers several potential practical advantages, and has contributed significantly to the development of polyelectrolyte multilayers in biomedical and biotechnological contexts.
The present invention relates to certain polyelectrolyte multilayers and methods that can be used to disrupt electrostatic interactions in such multilayers and promote the controlled disassembly of the multilayers in aqueous media.8,10 Methods that provide such control facilitate the development of thin films and coatings that permit the release of precise and well-defined quantities of chemical or biological agents from the surfaces of macroscopic, microscopic, or nanoscopic objects. The present invention provides a new approach to the design of polyelectrolyte multilayers that provides control over film erosion and the release of cationic agents from film-coated surfaces.
Several past studies have reported that it is possible to design polyelectrolyte multilayers that erode, degrade, or disassemble in aqueous environments by fabricating them using polyelectrolytes with functionality that can be cleaved or degraded, for example, either hydrolytically,11-16 enzymatically,17-19 or reductively.20,21 The incorporation of degradable polyelectrolytes permits tunable and/or triggered control over film disassembly and can be used to design films that provide control over the release of a variety of different agents.11-21 Additional details on these and other past approaches to promoting film disruption can be found in several recent reviews.8,10 The majority of past reports on the incorporation of degradable polymers into multilayered films have focused on the use of degradable cationic polymers and thus, in general, on films designed to erode and control the release anionic polyelectrolytes (e.g., DNA).8,10 
In principle, the fabrication of polyelectrolyte multilayers using degradable anionic polymers would provide a platform for the design of thin films that permit control over the release of cationic agents (e.g., cationic proteins, peptides, polymers, nanoparticles, etc.). There have been reports that enzymatically degradable anionic polymers can be used to fabricate multilayers that degrade in the presence of specific enzymes17,22 or upon contact with cells.17,23 Progress toward the fabrication of films using hydrolytically degradable anionic polymers, however, has been limited by the dearth of commercially available synthetic polymers that are both anionic and degradable, and, more generally, by the challenges associated with the synthesis of such polymers. Thus, there is a need in the art for synthetic polymers that are anionic and degradable.
It has been reported24-29 recently that it is possible to design ‘charge-shifting’ cationic polymers (that is, cationic polymers that undergo dynamic reductions in their net charge, which can also be called charge-dynamic polymers) by designing polymers inter alia with amine-functionalized side chains that can be cleaved hydrolytically. Polymer 1 (Eq 1) presents an example of this approach;24 this polymer undergoes a gradual reduction in net charge (e.g., from cationic to anionic) upon side chain hydrolysis. Polymer 1 can, for example, be used to fabricate multilayers that release plasmid DNA (negatively charged species) for up to three months.

Both film erosion and the release of DNA from mulitlayers containing polymer 1 can be understood in terms of disruptions in the ionic interactions in these assemblies that occur upon polymer side chain hydrolysis.24 Published U.S. patent application 2005/0027064 published Feb. 3, 2005 relates to charge-dynamic polymers and delivery of anionic compounds and provides additional examples of charge-dynamic polymer structures and their applications.